Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium.

OBJECTIVE: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. METHODS: CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. RESULTS: In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. CONCLUSIONS: Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.

Single incision laparoscopic surgery (SILS) versus conventional laparoscopic technique for ileostomy: a retrospective cohort study.

PURPOSE: Minimal-invasive surgery has gained wide acceptance in colorectal surgery. Single incision laparoscopic surgery (SILS) was designed to minimize surgical trauma and improve postoperative outcome. However, the role of SILS in ileostomy formation is unclear. METHODS: In this retrospective cohort study 26 patients were included. Six patients were operated with SILS and 20 with conventional laparoscopic technique for ileostomy. We retrospectively evaluated patient charts for baseline characteristics including prior abdominal surgeries and combination of surgeries. Our primary efficacy objectives were operation time and postoperative hospitalization days. Our safety objectives included the prevalence of postoperative pain, parastomal hernia, incisional hernia, perforation, wound infection, ileus, and infections in general. RESULTS: Baseline characteristics including previous abdominal surgery and concomitant surgeries were comparable in both groups. Total operation time using SILS (37.5 ± 6.2 min [mean ± SD]), compared to laparoscopic surgery (82.2 ± 54.8 min [mean ± SD]) was significantly shorter (p = 0.0002). In a sensitivity analysis excluding patients with combined surgery, ileostomy formation by SILS was shorter (36.5 ± 6.2 min [mean ± SD]), compared to laparoscopy (59.7 ± 28.7 min [mean ± SD]; p = 0.024). Length of postoperative stay was not statistically different between the groups (SILS: 5.5 ± 2.4 days [mean ± SD]; laparoscopic: 13.8 ± 17.3 days [mean ± SD], p = 0.193). Postoperative complication rates were low and comparable in both groups. CONCLUSION: Placement of a loop ileostomy using SILS technique not only reduces surgical trauma but also operation time without affecting postoperative hospital stay or postoperative complication rates. Single-incision laparoscopic surgery for ileostomy is an appealing approach for ileostomy in selected patients.

Checkpoint Inhibitor-Induced Colitis-A Clinical Overview of Incidence, Prognostic Implications and Extension of Current Treatment Options.

In recent years, anti-tumor immunotherapies have witnessed a major breakthrough with the emergence of immune checkpoint inhibitors (ICIs). However, the use of ICIs has also brought an era of a certain class of adverse events that differ from those of classical chemotherapies and are more reminiscent of autoimmune diseases. This article focuses exclusively on colitis as an irAE with emphasis on vulnerable patient groups, the prognostic significance of colitis, treatment, and new therapeutic approaches that may be applicable. Colitis itself is associated with a favorable oncological outcome of the underlying disease but is as well the most common irAE leading to discontinuation of therapy. Especially in vulnerable patient groups such as IBD patients and elderly patients, colitis occurs more frequently as a side effect. It is precisely in these two patient groups that side effects more often lead to discontinuation of therapy. Therefore, in addition to the current therapy of colitis through immunosuppression, the focus should also be on new forms of therapy of severe colitis, such as fecal transplantation or ileostomy creation.

Long-term immune-related adverse events after discontinuation of immunotherapy.

Immune checkpoint inhibitors have revolutionized the treatment of various cancers but are notorious for their potential to cause severe side effects. While most side effects occur during ongoing therapy, an increasing number of reports of late onset have emerged. It is also not yet clear how long side effects can last. Resolution is achieved under symptomatic therapy, but the side effects may persist latently. We present a patient case with recurrence of colitis after closure of an ileostomy over 1 year after discontinuation of immune checkpoint inhibitor therapy with nivolumab and ipilimumab. To the best of our knowledge, no other case with severe colitis still lasting after more than a year of suspension of therapy has yet been reported.

Lay abstract Checkpoint inhibitors have revolutionized therapy for suitable cancers. However, they can cause side effects that are reminiscent of autoimmune diseases. While most adverse effects occur during ongoing therapy, there are increasing reports of late-onset adverse effects after discontinuation of therapy and of long-lasting adverse effects after discontinuation of treatment, which may remain latent even if symptom relief could be achieved by immunosuppression. We present a patient case with reappearance of a severe inflammation of the large bowel (colitis) after closure of an ostomy over 1 year after withdrawal of immune checkpoint inhibitor therapy. To the best of our knowledge, no other case with severe colitis still lasting after more than a year of suspension of therapy has yet been reported.

Complete Recovery of Immune Checkpoint Inhibitor-induced Colitis by Diverting Loop Ileostomy.

Checkpoint inhibitor-induced side effects such as diarrhea and colitis occur in up to 30% of patients. We present a case of recurrent episodes of checkpoint inhibitor-induced colitis and subsequent Fournier gangrene that resolved after ileostomy formation. Once the Fournier gangrene and colitis had resolved, the ileostomy was reversed. However, within only 4 days, another serious flare-up of colitis occurred, necessitating emergent re-formation of the ileostomy. Expertise in the management of side effects of immune checkpoint inhibitor therapy is currently limited. Although most side effects are mild to moderate and transient, a minority of patients suffer from life-threatening complications, such as colitis. The creation of an ileostomy might be a valid treatment option in severe or recurrent colitis due to immune checkpoint inhibitor therapy. Intestinal diversion surgery may be useful if conservative treatment has failed, similar to other forms of immune-mediated intestinal inflammation.